POS1582 VEXAS SYNDROME: TWO CASES PRESENTING WITH PERIORBITAL EDEMA
Authors: M. R. Pozzi, A. DE Matthaeis, L. Bettini, V. Campanella, L. Riva, B. Scali, V. L’imperio, C. A. Scirè
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> VEXAS syndrome (vacuoles, E1enzyme, X-linked, autoinflammatory, somatic) is a X-linked autoinflammatory condition. The 3 most frequent somatic missense mutations affect methionine 41 of exon 3 (p.Met41Thr, p.Met41Val, p.Met41Leu) of ubiquitin-activating protein (UBA)1 gene, which encodes the E1 protein. Patients are usually men in their fifth-to-seventh decade of life and present with inflammatory symptoms, as well as hematologic manifestations with progressive bone marrow failure. <h3>Objectives</h3> We describe 2 patients with some key features that allow us to diagnose this syndrome. <h3>Results</h3> Case 1. AM, 78-year-old man, with chronic kidney disease. In August 2021 onset of left orbital inflammation, treated with antibiotics. A month later admission to our hospital for normocytic anemia, inflammation, oligoarthritis, moderate thrombocytopenia, superficial vein thrombosis and severe respiratory failure due to cryptogenic organizing pneumonia, which required ICU admission: no response to antibiotic therapy but to high dose iv steroid. He was discharged with oral prednisone (PDN), discontinued in three months. New hospitalization for headache, periorbital inflammation, diplopia, and right lateral gaze. No CNS involvement at brain CT-scan. Lab: Hb 9 g/dL, MCV 104 fl CRP 28 mg/dL, ESR 126 mm/h, ferritin 2710 ng/mL, fibrinogen 1142 mg/dL, creatinine 1.5 mg/dL. Normal levels of vitamin B12, folate, haptoglobin, LDH. Autoimmunity and microbiological work-up negative. MRI: bilateral orbital cellulitis, submandibular and parotid gland inflammation. PET-CT with <sup>18</sup>F-FDG: diffuse uptake in skeleton, spleen and in pulmonary left superior lobe. Bone marrow aspirate: no signs of myelodysplastic syndrome (MDS): vacuoles in the myeloid and erythroid series. UBA1 gene point mutation p.Met41* Val on bone marrow blood. PDN (0.75 mg/kg/day) was started with benefit on symptoms, anemia and inflammation. Mycophenolate mofetil was introduced as steroid sparing agent and PDN was tapered to 10 mg/day. Macrocytosis has not improved although Hb levels increased with normal reticulocyte count. CRP and ESR are normal and serum ferritin decreased. Case 2. SR, 70 years old man, in October 2021 he had superficial venous thrombosis of right leg, treated with LMWH. Two months later left leg deep venous thrombosis (DVT) and pulmonary thromboembolism, fever, arthritis, weight loss, elevation of CRP (23 mg/dL), Hb 13.3 g/dL with normal MCV. Apixaban and antibiotic were started. After the discharge, onset of periorbital edema with maxillary and ethmoid sinusitis and right arm DVT were diagnosed, and apixaban was changed into warfarin. Genetic and acquired thrombophilia were excluded. At <sup>18</sup>F-FDG PET scan diffuse increased uptake in bone marrow. Again periorbital edema and dysphagia. MRI: edema and solid tissue with contrast enhancement of left pyriform sinus without evidence of lymphadenopathy. ER admission for urticarial rash, fever, and severe chest pain due to pericarditis: elevated CRP, and macrocytic anemia (Hb 9.5 g/dl, MCV 107 fl) with normal folic acid and B12 vitamin. Infections and CTD were ruled out. Bone marrow biopsy findings were coherent with MDS. Though vacuoles absence, UBA1 pMet41Val missense mutation was found. PDN 1 mg/kg/day with subsequent tapering was started with clinical improvement, normalization of acute phase reactants and Hb concentration (13.8 g/dl), but persistent macrocytosis. The subsequent needed dose of PDN was &gt; 25 mg/day and the patient is a candidate for 5-Azacytidine therapy. <h3>Conclusion</h3> The VEXAS syndrome increased the awareness of complex associations between MDS and adult-onset inflammatory conditions. In our experience recurrent periorbital edema could be a clinical clue for this syndrome. Macrocytic anemia appeared with persisting inflammation after some months and supports the link between inflammation and MDS development; nevertheless macrocytosis remain stable irrespective of clinical and acute phase reactants improvement. Finally,the lack of vacuolization on bone marrow biopsy should not preclude a search of UBA1 gene mutation. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.